title: RTP801/REDD1 regulates the timing of cortical neurogenesis and neuron migration.
abstract: The generation, differentiation, and migration of newborn neurons are critical features of normal brain development that are subject to both extracellular and intracellular regulation. However, the means of such control are only partially understood. Here, we show that expression of RTP801/REDD1, an inhibitor of mTOR (mammalian target of rapamycin) activation, is regulated during neuronal differentiation and that RTP801 functions to influence the timing of both neurogenesis and neuron migration. RTP801 levels are high in embryonic cortical neuroprogenitors, diminished in newborn neurons, and low in mature neurons. Knockdown of RTP801 in vitro and in vivo accelerates cell cycle exit by neuroprogenitors and their differentiation into neurons. It also disrupts migration of rat newborn neurons to the cortical plate and results in the ectopic localization of mature neurons. On the other hand, RTP801 overexpression delays neuronal differentiation. These findings suggest that endogenous RTP801 plays an essential role in temporal control of cortical development and in cortical patterning.
authors.affiliation: Department of Pathology and Cell Biology, Columbia University College of Physicians and Surgeons, New York, New York 10032, USA. cristina.malagelada@ub.edu
authors.forename: Cristina
authors.initials: C
authors.lastname: Malagelada
authors.forename: Miguel Angel
authors.initials: MA
authors.lastname: López-Toledano
authors.forename: Ryan T
authors.initials: RT
authors.lastname: Willett
authors.forename: Zong Hao
authors.initials: ZH
authors.lastname: Jin
authors.forename: Michael L
authors.initials: ML
authors.lastname: Shelanski
authors.forename: Lloyd A
authors.initials: LA
authors.lastname: Greene
mesh_terms: D000818:Animals; D019521:Body Patterning / Q000235:genetics / Q000502:physiology; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology; D002465:Cell Movement / Q000235:genetics / Q000502:physiology*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000502:physiology*; D055785:Gene Knockdown Techniques; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D055495:Neurogenesis / Q000235:genetics / Q000502:physiology*; D009474:Neurons / Q000166:cytology* / Q000502:physiology*; D016716:PC12 Cells; D051381:Rats; D012097:Repressor Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D013234:Stem Cells / Q000166:cytology / Q000502:physiology; D013997:Time Factors; D014157:Transcription Factors
chemical_list: C000632146:Ddit4 protein, rat; D012097:Repressor Proteins; D014157:Transcription Factors